Search For The Functions That Mediate Protein Palmitoylation And Depalmitoylation

<p>Protein palmitoylation is a critical regulator of protein location, function and activity in the cell. While it has been known for some time that proteins can have cycles of palmitoylation and depalmitoylation throughout their lifetime, a thioesterase responsible for mediating the bulk of these depalmitoylation reactions has remained elusive. Described here is the development and implementation of genomic screens in <i>Saccharomyces cerevisiae</i> aimed at identifying gene products responsible for this activity. While many candidates were isolated from this analysis, especially those whose cellular function involves polarized cell growth and morphogenesis, two candidates were chosen for additional characterization. The first of these, Bch2, is a component of the yeast exomer complex, which is responsible for trafficking specific proteins from the <i>trans</i>-Golgi network to the plasma membrane. Bch2 was the strongest candidate from screens of two different overexpression libraries and <i>BCH2</i> overexpression decreases the amount of palmitoylated Yck2 in palmitoylation assays. Results presented here show that <i>BCH2</i> overexpression disrupts exomer complex function, which underlies the defect in palmitoylation of Yck2. A model proposed here suggests that upon proper function of the exomer complex, a thioesterase depends on this pathway for delivery to the plasma membrane. Disruption of this pathway leads to accumulation of the thioesterase in the Golgi, the site of Yck2 palmitoylation and thereby mediates the decrease in palmitoylated Yck2. Additionally, the yeast protein YBR096w, a weaker candidate from the genomic screens was also characterized. This protein has several potential lipidation sites and a thioesterase domain, characteristics it shares with known thioesterases.</p>

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

WSU Access

Discipline thesis:degree_discipline

Pharmacology

Year dc:date.available

2010

Author dc:creator

• Prior, Margaret

Contributors dc:contributor

• Nicholas G. Davis

• Genetic screen
• Protein Depalmitoylation
• Protein Palmitoylation
• Thioesterase
• Yck2
• Cell Biology

Repository record dc:identifier

https://digitalcommons.wayne.edu/oa_dissertations/27

OAI identifier oai:identifier

oai:digitalcommons.wayne.edu:oa_dissertations-1026